Red face related skin disorders, which share symptomatic similarities and probably pathological causes, include rosacea, acne vulgaris, seborrheic dermatitis, photodermatitis and contact dermatitis. These red face related conditions may range from feelings of heat and sensitivity to flushing or burning with intense sensitivity. Patients with red face related skin disorders often exhibit extreme sensitivity to environmental and topical factors. Steroid-induced rosacea-like dermatitis (or steroid rosacea) is a papular or pustular lesions with erythematous and edematous base with or without telangiectasia, which is caused by prolonged application of topical steroids to the face or as a rebound condition after discontinuation of topical steroids.
Dermatologic toxicities are known cutaneous adverse events associated with targeted therapies or immunotherapy and share similar symptoms and probable pathologic causes of the red face-related skin disorders. Targeted therapies such as epidermal growth factor receptor (EGFR), multityrosine kinase (MTK), MEK, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and BRAF inhibitors could induce toxicities including papulopustular rash, maculopapular rash, erythema, telangiectasias flushing, paronychia and fissure, hair changes, xerosis, mucositis, pruritus, and hand-foot skin reaction, which may occur in more than 90% of patients and may also superinfected with bacteria, such as staphylococcus aureus. (Wollenberg A, Kroth J et al, 2010; Lacouture M E, Maitland M L et al, 2010; Curry J. L., Torres-Cabala C. A., et al., 2014). Histopathologic findings of such skin toxicities showed that inflammation is frequently involved and leads to acneiform skin rash. A papulopustular rash was more frequently reported on EGFR inhibitors like cetuximab (83% of patients) and afatinib (90% of patients), and MEK inhibitors like selumetinib (93% of patients) and trametinib (80% of patients) therapy. A maculopapular rash was more commonly described with PI3K inhibitors like BKM-120 (37% of patients) and MK2206 (52% of patients) therapy.
Berberine (Natural Yellow 18, 6-dihydro-9,10-dimethoxybenzo(g)-1,3-benzodioxolo (5,6-a) quinolizinium) is an isoquinoline alkaloid present in herb plants, such as coptis (Coptidis rhizome), phellodenron, Scutellaria baicalensis, Mahonia aquifolium and berberis. Berberine and its derivatives have been found to have antimicrobial and antimalarial activities. It can act against various kinds of pathogens such as fungi, saccharomycete, parasite, bacterium and virus.
Berberine also has anti-inflammatory function, yet the exact mechanism is unknown.
U.S. Pat. No. 6,440,465 pertains to topical skin formulations of glucosamine in an emollient base which contains berberine for the treatment of psoriasis. U.S. Patent Application Publication No. 20050158404 pertains to a nutritional product, dietary supplement or pharmaceutical composition which contains vitamin A, vitamin E, selenium, vitamin B6, zinc, chromium, and a herbal source of berberine for the treatment of acne in oral administration. U.S. Pat. No. 6,974,799 relates to topical compositions comprising a tripeptide (N-palmitoyl-Gly-His-Lys) and a tetrapeptide (N-palmitoyl-Gly-Gln-Pro-Arg) for the treatment of visible signs of aging including wrinkles, stretch marks, dark circles. The formulation may contain additional ingredients, including berberine. In these inventions, berberine is included as one of the many ingredients and its concentration is not specified.
US Patent Application Publication No. 2004/0146539 relates to topical nutraceutical compositions with body slimming and tone-firming anti-aging benefits that may be used to treat skin aging, skin wrinkle, skin exfoliating, acne, rosacea and other skin problems. The composition of this invention includes antimicrobial agents selected from several agents including berberine. In these nutraceutical compositions, berberine is included as one of the many ingredients and its concentration is not specified. There has been a 10% Mahonia aquifolium cream (Relieva™, Apollo Pharmaceutical Canada Inc) containing 0.1% berberine for the treatment of psoriasis.
US Patent Application Publication No. 2012/0165357 discloses the use of berberine to treat various red face related skin disorders but it does not disclose any specific formulations of berberine that would be found to be effective for the treatment of specific conditions. Further, it is known that berberine cannot easily efficiently penetrate the skin, and therefore it is likely to be instantly released into the tissue resulting in a temporary effect.
Therefore, there is still a need to develop new effective formulations of berberine for the treatment of various red face related skin disorders.